Summary Dysregulated IL-1β and IL-6 responses have been implicated in the pathogenesis of severe Coronavirus Disease 2019 (COVID-19). Innovative approaches for evaluating the biological activity of these cytokines in vivo are urgently needed to complement clinical trials of therapeutic targeting of IL-1β and IL-6 in COVID-19. We show that the expression of IL-1β or IL-6 inducible transcriptional signatures (modules) reflects the bioactivity of these cytokines in immunopathology modelled by juvenile idiopathic arthritis (JIA) and rheumatoid arthritis. In COVID-19, elevated expression of IL-1β and IL-6 response modules, but not the cytokine transcripts themselves, is a feature of infection in the nasopharynx and blood but is not associated with severity of COVID-19 disease, length of stay, or mortality. We propose that IL-1β and IL-6 transcriptional response modules provide a dynamic readout of functional cytokine activity in vivo , aiding quantification of the biological effects of immunomodulatory therapies in COVID-19. Graphical Abstract Highlights • Transcriptional response modules reflect IL-1β and IL-6 activity in vivo • Response modules are superior to single gene transcripts in measuring cytokine activity • Elevated IL-1β and IL-6 activity is a feature of COVID-19 disease in blood and tissues • COVID-19 disease severity is not associated with greater IL-1β or IL-6 activity Immunology; Virology; Transcriptomics
【저자키워드】 immunology, Virology, transcriptomics, 【초록키워드】 COVID-19, clinical trial, Pathogenesis, Mortality, IL-6, Infection, complement, cytokine, immunopathology, rheumatoid arthritis, COVID-19 disease, severity of COVID-19, response, nasopharynx, quantification, disease, expression, Blood, juvenile idiopathic arthritis, immunomodulatory therapy, IL-1β, therapeutic targeting, Bioactivity, tissue, COVID-19 disease severity, transcriptional response, single gene, biological activity, transcript, Effect, approach, transcriptional, greater, elevated, functional, implicated, reflect, 【제목키워드】 COVID-19, IL-6, IL-1β,